Abstract The purpose of this New Innovator research is to move beyond the limited notion of the placebo effect as some mysterious response to an inert substance toward the recognition that ultimately our mindsets (e.g., beliefs and expectations) are responsible for these responses. The idea of a ?placebo response? has been recognized for centuries yet has typically been marginalized from mainstream medicine as something to be ignored or controlled for. Yet the power of placebos?more usefully expressed as the power of conscious or subconscious mindsets?is becoming increasingly difficult to deny. Advances in research illuminate that mindsets influence health through precise neurobiological mechanisms without the aid of treatment (placebo treatments have proven to be effective in a number of conditions ranging from pain and depression to cardiovascular disease and Parkinson's disease) and they also moderate the effectiveness of active drugs and therapies (drugs and therapies given without the patient's awareness or expectation to heal can be up to 90% less effective than when the patient fully expects to experience the effect of the drug or therapy). Furthermore, our research has demonstrated that placebo-like mindset effects also play a role in determining the benefits of behavioral therapies such as exercise, diet and stress. As the major health threats of the 21st century move away from infectious disease towards non-communicable or chronic diseases (e.g. obesity, heart disease, mental illness, diabetes), understanding these effects becomes increasingly more important. This research focuses on the influence and effect of mindset in various stages related to chronic disease. First we will conduct innovative research aimed at better understanding of the role of mindset in the expression of chronic disease by a) discover the impact of mindsets about genetic predisposition for chronic disease on the ultimate expression of those genes, a topic that is increasingly relevant in this day of ?personalized medicine?; b) advancing our understanding of the impact of mindset in determining the effects of health behaviors such as exercise, diet and stress; and c) expand the meaning of health to include more compelling and enriching definitions. Second, we intend to empower and enable individuals and healthcare practitioners to harness mindsets in the prevention and treatment of chronic disease by a) developing and testing innovative methods to change mindsets in non-deceptive and ethically appropriate ways; and b) understanding and overcoming barriers for health practitioners to incorporate mindset change in 21st century healthcare.